ABSTRACT:
The current global pandemic (COVID-19) and other recent major epidemics, including SARS and MERS and the historical Spanish flu, are caused by respiratory viruses that affect the lung. To better understand the pathophysiology of these diseases and develop preventive and therapeutic measures, translational models play a key role in the pathway toward clinical trials and range from simple cell cultures through 3D organoids to animal models. On the one hand, animal models are a standard method before human clinical trials, but these suffer from ethical concerns and physiological differences. On the other hand, 2D and even 3D cell cultures, such as organoids, are easier to work with and significantly cheaper. Still, they often fail to recapitulate the complexity of the in vivo situation (blood vessels, nerves, and lymphoid tissue and
contraction)
Another advantage of this methodology is that the tissue models can be created with primary cells from individual patients to develop personalized medicine approaches, as currently done for cancer therapeutics. This project addresses the development of 3D in vitro models of airway tissues with varying complexity levels to be used in understanding and treating not only COVID-19 and its variants in the short term but potentially any respiratory disease in the long term. For its development, some steps that will be carried out include the combination of biocompatible hydrogel materials with co-culture of relevant cells to mimic the airway epithelium and stroma, the fabrication by electrospinning of a porous membrane that works as a support for the cells the development of 3D microfluidic devices fabricated using rapid prototyping technologies such as stereolithography, and integration of these devices into bioreactors to enable dynamic culturing, delivery of model compounds, and 4D characterization and data analysis as proof of concept for studying mechanisms of viral infection and development of treatments.